METHODS: RNA transcriptome analyses were performed on platelets purified from SFTS patients and SFTSV-infected mice. The functions of differentially expressed genes (DEGs) in the platelets were characterized. ELISA, flow cytometry, and qRT-PCR were used to measure the levels of platelet activation, SFTSV infection in platelets, formation of neutrophil extracellular traps (NETs), transcription of DEGs and percent of platelets undergoing cell death.
RESULTS: Enhanced neutrophil activation and interferon (IFN) signaling involved in the viral life cycle were common platelet responses in SFTS, which may consume increasing numbers of platelets. Other functional changes may be associated with different outcomes of SFTS. SFTSV infection led to platelet destruction by pyroptosis, apoptosis, necroptosis, and autophagy. In contrast to SFTS patients, platelets in SFTSV-infected mice mainly play a role in adaptive immunity, and platelet death was not as severe as in humans.
CONCLUSIONS: The altered functions of platelets, such as mediating leukocyte activation and undergoing cell death, contribute to thrombocytopenia in SFTS patients. The different mechanisms of thrombocytopenia in mice, suggest that platelet functions should be considered in experimental animal models.
方法:对从SFTS患者和SFTSV感染小鼠纯化的血小板进行RNA转录组分析。对血小板中差异表达基因(DEGs)的功能进行了表征。ELISA,流式细胞术,和qRT-PCR用于测量血小板活化水平,血小板SFTSV感染,中性粒细胞胞外陷阱(NET)的形成,DEGs的转录和经历细胞死亡的血小板百分比。
结果:病毒生命周期中中性粒细胞活化和干扰素(IFN)信号增强是SFTS中常见的血小板反应,这可能会消耗越来越多的血小板。其他功能变化可能与SFTS的不同结果相关。SFTSV感染通过焦亡导致血小板破坏,凋亡,坏死,和自噬。与SFTS患者相比,SFTSV感染小鼠的血小板主要在适应性免疫中起作用,血小板死亡没有人类那么严重。
结论:血小板功能的改变,如介导白细胞活化和细胞死亡,导致SFTS患者血小板减少。小鼠血小板减少的不同机制,建议在实验动物模型中应考虑血小板功能。